The induction of apoptosis in PC12 cells by the enediyne neocarzinostatin (NCS) is paradoxically potentiated by overexpression of bcl-2. The enhanced activation of NCS seen in bcl-2-overexpressing cells cannot by itself be responsible for the potentiation of apoptosis, since Bcl-2 would be expected to block apoptosis at a point distal to NCS activation (e.g., in the apoptosis final common pathway). We now report that overexpression of bcl-2 in PC12 cells does not protect the cells from NCS-induced oxidation of membrane phosphatidylserine (PS), and results in potentiation of NCS-induced externalization of membrane PS, two events associated with the apoptosis final common pathway. The mechanism of potentiation of apoptosis by Bcl-2 is related to the enhanced reducing potential of bcl-2-overexpressing PC12 cells.
Copyright 1999 Elsevier Science B.V.